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Transition Metal Complexes as Drugs and Chemotherapeutic Agents

  • Kartonierter Einband
  • 304 Seiten
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When this book was first conceived as a project the expanding interest in the clinical use of platinum and gold complexes made a s... Weiterlesen
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Beschreibung

When this book was first conceived as a project the expanding interest in the clinical use of platinum and gold complexes made a survey of the relevant biological properties of metal complexes timely and appropriate. This timeliness has not diminished during the gestation and final publica tion of the manuscript. The introduction contains an explanation of the layout and approach to the book, which I wrote as an overall survey of the wide variety of biological properties of metal complexes. Hopefully, the reader will see the parallels in mechanisms and behavior, even in different organisms. The writing was considerably helped by the enthusiasm and confidence (totally unearned on my part) in the project of Professor Brian James and lowe him my special thanks. I also owe a great debt of gratitude to my colleagues, and especially to Eucler Paniago, of the Universidade Federal de Minas Gerais, for their comprehension and for the initial leave of absence which allowed me to begin the project. To those who read some or all of the manuscript and made suggestions, Bernhard Lippert, Kirsten Skov, and Tom Tritton, as well as the editor's reviewer I am also grateful. As usual, the final responsibility for errors or otherwise rests with the author.

Inhalt
Metals in Medicine.- Chemotherapeutic Agents and Drugs.- Mechanisms of Toxicity.- Metal Accumulation and Activation.- Biochemical Targets for Metal Complexes.- Summary.- References.- 1. Interaction of Metal Complexes with DNA.- 1.1. DNA and Conformation.- 1.1.1. Nucleases and DNA.- 1.2. Experimental Methods for the Study of Conformational Changes.- 1.2.1. Uvltraviolet Spectroscopy.- 1.2.2. Circular Dichroism and Optical Dispersion.- 1.2.3. Nuclear Magnetic Resonance.- 1.2.4. Hydrodynamic and Light Scattering Properties.- 1.3. Binding of Metal Complexes to DNA.- 1.3.1. Intercalation.- 1.3.1.1. PlatinumTerpyridine Complexes.- 1.3.1.2. Metal(1, 10-Phenanthroline) Complexes.- 1.3.1.3. Porphyrins and Metalloporphyrins.- 1.3.1.4. Intercalators as Drugs.- 1.3.1.5. Redox Activity of Metallointercalators.- 1.3.2. Outer Sphere Binding.- 1.3.2.1. MetalAmine Complexes.- 1.3.3. Inner Sphere (Covalent) Binding.- 1.3.3.1. Binding of PlatinumAmine Complexes.- 1.3.3.2. PlatinumAmine Complexes and Intercalators.- 1.3.3.3. Restriction Enzymes and Platinum Complexes.- 1.3.4. Strand Breakage.- 1.3.4.1. Copper(1, 10-phenanthroline) Complexes.- 1.3.4.2. Cobalt(1, 10-phenanthroline) Complexes.- 1.3.4.3. IronEDTA(DNA-binder) Complexes.- 1.4. Summary.- References.- 2. PlatinumAmine Complexes as Anticancer Agents.- 2.1. The Discovery of Cisplatin as an Antitumour Agent.- 2.2. Clinical Properties of Cisplatin.- 2.3. Development of Cisplatin Analogues.- 2.3.1. Clinical trials of Cisplatin Analogues.- 2.4. Biochemical Mechanism of Action of Platinum Complexes.- 2.4.1. Biological Effects Implying DNA as Target.- 2.4.2. Biological Effects not Involving DNA.- 2.5. Summary.- References.- 3. StructureActivity Relationships of Platinum Amine Complexes.- 3.1. The Requirement for Neutrality.- 3.2. Complexes of Pt(IV).- 3.3. Nature of the Leaving Group.- 3.3.1. Bisplatinum Complexes Containing Bridging Dicarboxylates.- 3.3.2. Sulfoxides as Leaving groups.- 3.4. Nature of the Nonleaving Group.- 3.4.1. Stereospecific Effects in Amine Complexes.- 3.5. Novel and Targeted Approaches to [PtX2(am)2] Complexes.- 3.5.1. Ternary Complexes.- 3.5.2. Amines as Carrier Ligands.- 3.6. Quantitative StructureActivity Relationships.- 3.7. Chemistry of PlatinumAmine Complexes.- 3.7.1. Reactions with Biomolecules Other Than DNA.- 3.8. Summary.- References.- 4. Interactions of Platinum Complexes with DNA Components.- 4.1. Structural Aspects of MetalNucleobase Binding.- 4.1.1. Binding in Solution.- 4.1.1.1. Basicity and pH.- 4.1.1.2. HardSoft Relationship of Donor Atom and Metal Ion.- 4.1.1.3. Steric Effects Including Hydrogen Bonding.- 4.1.1.4. Base Stacking and Chelation.- 4.1.2. Binding of Platinum Complexes in Solution.- 4.2. Reactivity of Platinum MetalBase Complexes.- 4.2.1. Effect of Metallation on Acidity of Noncoordinated Atoms.- 4.2.1.1. The PlatinumN7, O6 Chelate.- 4.2.2. Effect of Metallation on CH Exchange.- 4.2.3. Susceptibility to Oxidation of MetalBase Complexes.- 4.2.4. Reactivity of Nucleoside and Nucleotide Linkages.- 4.2.5. Reactivity of MetalBase Complexes toward Nucleophiles.- 4.2.6. Linkage Isomerization.- 4.2.7. Rotation around MetalPurine Bonds.- 4.3. Solid State Structural Studies.- 4.4. Structural Studies on Di- and Oligonucleotide Complexes.- 4.4.1. Studies on Dinucleotide Complexes.- 4.4.2. Studies on Trinucleotides.- 4.4.3. Studies on Oligonucleotides.- 4.4.3.1. Structural Studies on Oligonucleotides.- 4.5. Platinum Adducts from DNA Degradation.- 4.6. On the Molecular Mechanism of Antitumour Action of Cisplatin.- 4.7. Summary.- References.- 5. The PlatinumPyrimidine Blues.- 5.1. Properties of the PlatinumPyrimidine Blues.- 5.2. Platinum Blues not Derived from Pyrimidines.- 5.3. X-Ray Structure of PlatinumPyrimidine and ?-Pyridone Blues.- 5.4. Formation of PlatinumPyrimidine and ?-Pyridone Blues.- 5.4.1. Monomeric Complexes.- 5.4.2. Dimeric Complexes.- 5.4.3. Complexes of Pt(III).- 5.5. Studies of Crystalline Blues.- 5.6. Biological Studies on PlatinumPyrimidine Blue Precursors.- 5.7. Summary.- References.- 6. Antitumour Activity of Metal Complexes.- 6.1. Platinum Group Metal Complexes.- 6.1.1. Palladium Complexes.- 6.1.2. Rhodium Complexes.- 6.1.2.1. Studies on Rhodium Carboxylates.- 6.1.3. Ruthenium Complexes.- 6.1.3.1. Studies on RutheniumAmine Complexes.- 6.2. Copper Complexes.- 6.2.1. Bis(Thiosemicarbazone) Complexes.- 6.2.2. Thiosemicarbazone Complexes.- 6.2.3. Nitrogen Chelates.- 6.2.4. Copper Salicylates.- 6.3. Silver and Gold.- 6.4. Organometallic Complexes.- 6.5. Summary.- References.- 7. Metal-Mediated Antibiotic Action.- 7.1. Discovery and Pharmacology of Bleomycin.- 7.2. Structure of Bleomycin and Analogues.- 7.3. Metal Complexes of Bleomycin.- 7.3.1. Copper Bleomycin.- 7.3.2. Cobalt Bleomycin.- 7.3.3. Manganese Bleomycin.- 7.4. Mechanism of Action of Bleomycin.- 7.4.1. DNABleomycin Interactions.- 7.4.2. Iron and IronOxygen Adducts.- 7.5. Other Metal Binding Antibiotics.- 7.5.1. Anthracyclines.- 7.5.1.1. Biochemical Aspects of MetalAnthracyclines.- 7.5.2. Streptonigrin.- 7.6. Summary.- References.- 8. Metals, Metal Complexes, and Radiation.- 8.1. Interaction of Radiation and Biological Tissue.- 8.2. Chemical Modification of Radiation Damage.- 8.2.1. Oxygen Mimics and Electron Affinity.- 8.3. Metal Complexes as Radiation Sensitizers.- 8.3.1. Radiosensitization by Metal Salts.- 8.3.2. CobaltAmine Complexes.- 8.3.3. Radiosensitization by Electron Affinity.- 8.3.3.1. MetalRadiosensitizer Complexes.- 8.3.3.2. Metal Chelates.- 8.3.4. Potentiation of Radiation Damage by PlatinumAmines. Differential Repair Processes.- 8.3.4.1. Mechanism of Action of PlatinumAmine Complexes.- 8.3.5. Radiosensitization by Thiol Depletion.- 8.4. Metal Complexes and Radioprotection.- 8.4.1. Metal Complexes as Radioprotectors.- 8.5. Activation of Metal Complexes.- 8.6. Summary.- References.- 9. Antibacterial Effects of Metal Complexes.- 9.1. Mercury and Silver Salts as Antibacterial Agents.- 9.1.1. Mercury.- 9.1.2. Silver.- 9.2. Antibacterial Activity of Chelating Agents and Metal Chelates.- 9.3. Antibacterial Activity of MetalAmine Complexes.- 9.4. Redox Activity and Antibacterial Activity.- 9.5. Summary.- References.- 10. Antiviral and Antiparasitic Effects of Metal Complexes.- 10.1. Antiviral Therapy.- 10.2. Chelating Agents and Metal Complexes as Antiviral Agents.- 10.2.1. Chelating Agents.- 10.2.2. Metal(1, 10-Phenanthroline) Complexes.- 10.2.3. Platinum and PalladiumAmine Complexes.- 10.2.4. Zinc Complexes.- 10.2.5. Other Metal Complexes.- 10.3 Metal Complexes as Antiprotozoal Agents.- 10.3.1. Metal Complexes in Trypanosomiasis.- 10.3.2. PlatinumAmine Complexes as Trypanocides.- 10.3.3. Other Metal Complexes.- 10.3.4. Porphyrins and Metalloporphyrins as Trypanocides. Metal Sequestration.- 10.3.5. Metal Complexes with Trypanocidal Drugs. Dual-Function Agents.- 10.3.6. Metal Complexes in American Trypanosomiasis.- 10.4. Summary.- References.- 11 Metal Complexes in Arthritis.- 11.1. Gold Complexes in the Treatment of Rheumatoid Arthritis.- 11.1.1. Activity and Toxicity of Gold Drugs.- 11.1.2. Structures of Gold Complexes.- 11.1.3. Chemistry and Biochemistry of Gold Drugs.- 11.1.4. Mechanism of Action of Gold Drugs.- 11.2. Copper in Arthritis.- 11.2.1. Copper Complexes in Arthritis.- 11.2.2. Copper Bracelets.- 11.2.3. Copper and D-Penicillamine.- 11.2.4. Mechanism of Action of Copper Complexes.- 11.3. Other Metals.- 11.4. Summary.- References.- 12. Miscellaneous Uses of Metal Complexes.- 12.1. Mercurial Diuretics.- 12.2. Neuromuscular Effects of Metal Complexes.- 12.3. Nitroprusside as Vasodilator.- 12.3.1. Activity and Toxicity of Nitroprusside.- 12.3.2. Mechanism of Action of Nitroprusside.- 12.4. Summary.- References.- Names and Abbreviations.- Glossary of Terms and Definitions.- Appendix 1.- Appendix 2.- Index of Subjects.

Produktinformationen

Titel: Transition Metal Complexes as Drugs and Chemotherapeutic Agents
Autor:
EAN: 9789401175708
ISBN: 9401175705
Format: Kartonierter Einband
Herausgeber: Springer Netherlands
Genre: Chemie
Anzahl Seiten: 304
Gewicht: 443g
Größe: H229mm x B152mm x T16mm
Jahr: 2012
Untertitel: Englisch
Auflage: Softcover reprint of the original 1st ed. 1989

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